Mercaptopurine

Mercaptopurine, also known as 6-mercaptopurine (6-MP), is a purine analog antimetabolite used as chemotherapy and an immunosuppressant. It is employed in the treatment of acute lymphoblastic leukemia (ALL), particularly in maintenance therapy, and is also used in inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, as well as in some immunosuppressive regimens for organ transplantation.

Mechanism of action involves conversion by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) to active thioinosinic and thio-guanylate nucleotides. These metabolites inhibit de novo purine synthesis and are incorporated into RNA and DNA, leading to impaired replication and reduced proliferation of rapidly dividing cells, especially lymphocytes.

Metabolism and pharmacogenetics are important considerations. 6-MP is inactivated by xanthine oxidase and is also processed by thiopurine methyltransferase (TPMT). Genetic variations in TPMT affect drug tolerance; individuals with low TPMT activity are at higher risk of severe myelosuppression. Co-administration of allopurinol can markedly increase 6-MP levels by inhibiting XO, often requiring dose reduction.

Administration typically occurs orally, with dosing based on body surface area or weight and as part of broader regimens. Azathioprine, a related prodrug, is converted to 6-MP in the body and shares similar metabolic pathways and toxicities.

Adverse effects include bone marrow suppression, hepatotoxicity, pancreatitis, nausea, vomiting, and mucositis, along with increased infection risk due to immunosuppression. Monitoring usually involves regular complete blood counts and liver function tests, with dose adjustments as needed.